Progressive muscle weakness: More there than meets the eye
BACK TO OUR PATIENT
Our patient’s further laboratory results are listed in Table 3.
She has elevated 24-hour urinary cortisol excretion, consistent with Cushing syndrome. Her corticotropin level is elevated, which rules out an adrenal cause. Her 5-HIAA (a serotonin breakdown product) and calcitonin levels are also elevated, suggesting either medullary thyroid cancer or a carcinoid tumor. She also has a mild elevation of dehydroepiandrosterone sulfate, which is consistent with corticotropin-dependent Cushing syndrome.
Our patient’s elevated levels of cortisol were the cause of her muscle weakness and severe immune deficiency, which in turn led to cytomegalovirus viremia and sepsis. Cushing syndrome usually causes hypertension, especially in cases of ectopic corticotropin production. However, our patient was normotensive on admission and then developed cytomegalovirus sepsis, which led to hypotension and shock.
Immune suppression is a well-known effect of glucocorticoids.26–28 Kronfol et al28 found that CD4 and CD8 counts and the CD4-to-CD8 ratio were low in patients with Cushing syndrome, and natural killer cell activity was suppressed. Opportunistic infections have been described in patients with Cushing syndrome.26,27,29
MANAGEMENT OF CUSHING SYNDROME
Management of Cushing syndrome should be tailored after determining its source.
A neurosurgical consultation is warranted in cases of pituitary adenoma, with surgical resection of the adrenal source or ectopic tumor if feasible.25
Medical management is recommended if surgical resection is not possible.30,31 Several drugs can be used to inhibit cortisol synthesis in this situation.30,32
Adrenal-acting agents
Aminoglutethimide (Cytadren) acts by blocking the conversion of cholesterol to pregnenolone, a precursor of cortisol. The dosage is 250 mg twice or three times a day. This drug is no longer available in the United States.
Ketoconazole (Nizoral) inhibits side-chain cleavage, 11-beta hydroxylase, and 17-alpha hydroxylase, thus inhibiting cortisol synthesis; it also inhibits corticotropin secretion. The dosage is 200 to 400 mg three times a day.
Metyrapone (Metopirone) blocks 11-beta-hydroxylation of deoxycortisol, the reaction that produces cortisol. The dosage is 500 to 750 mg three times a day. This drug can be obtained only from the manufacturer and only on a named-patient basis.
Etomidate (Amidate), an anesthetic drug, also blocks 11-beta-hydroxylation of deoxycortisol. It is given intravenously at a rate of 0.3 mg/kg per hour.
Centrally acting agents
Cabergoline (Dostinex). It is believed that corticotropin-producing pituitary tumors express D2 receptors. Cabergoline is a dopamine agonist that has been used in patients with Cushing disease. The dosage is 0.5 to 7 mg/week.
Pasireotide is still investigational. It is a somatostatin receptor agonist given subcutaneously for 15 consecutive days to patients with Cushing disease.
Glucocorticoid receptor antagonist
Mifepristone (Mifeprex) is a progesterone receptor and glucocorticoid II receptor antagonist that is being investigated in the treatment of persistent or recurrent Cushing disease. It is not yet approved by the US Food and Drug Administration for this indication.
BACK TO OUR PATIENT
The patient was too ill to undergo additional imaging, including octreotide scanning to identify an ectopic corticotropin-secreting tumor. She was medically treated with intravenous etomidate to reduce her cortisol level.30,31
Unfortunately, our patient died of multiorgan failure. The exact site of her ectopic corticotropin-producing tumor was never identified, and no autopsy was done.
